The mechanism of safrole-induced [Ca 2+ ]i rises and Non-Ca 2+ -triggered cell death in SCM1 human gastric cancer cells

Tzu Yi Hung, Chiang Ting Chou, Te Kung Sun, Wei Zhe Liang, Jin Shiung Cheng, Yi Chien Fang, Yih Do Li, Pochuen Shieh, Chin Man Ho, Chun Chi Kuo, Jia Rong Lin, Daih Huang Kuo, Chung Ren Jan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

2 Scopus citations

Abstract

Safrole is a carcinogen found in plants. The effect of safrole on cytosolic free Ca 2+ concentrations ([Ca 2+ ]i) and viability in SCM1 human gastric cancer cells was explored. The Ca 2+ -sensitive fluorescent dye fura-2 was applied to measure [Ca 2+ ]i. Safrole at concentrations of 150-450 μM induced a [Ca 2+ ]i rise in a concentration-dependent manner. The response was reduced by 60% by removing extracellular Ca 2+ . Safrole-evoked Ca 2+ entry was not altered by nifedipine, econazole, SKF96365, and protein kinase C activator or inhibitor. In Ca 2+ -free medium, treatment with the endoplasmic reticulum Ca 2+ pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) abolished safrole-evoked [Ca 2+ ]i rises. Conversely, treatment with safrole abolished thapsigargin or BHQ-evoked [Ca 2+ ]i rises. Inhibition of phospholipase C (PLC) with U73122 abolished safrole-induced [Ca 2+ ]i rises. At 250-550 μM, safrole decreased cell viability concentration-dependently, which was not reversed by chelating cytosolic Ca 2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid/acetoxy methyl (BAPTA/AM). Annexin V/propidium iodide staining data suggest that safrole (350-550 μM) induced apoptosis concentration-dependently. These studies suggest that in SCM1 human gastric cancer cells, safrole induced [Ca 2+ ]i rises by inducing PLC-dependent Ca 2+ release from the endoplasmic reticulum and Ca 2+ influx via non-store-operated Ca 2+ entry pathways. Safrole-induced cell death may involve apoptosis.

Original languageEnglish
Pages (from-to)302-311
Number of pages10
JournalChinese Journal of Physiology
Volume58
Issue number5
DOIs
StatePublished - 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 by The Chinese Physiological Society and Airiti Press Inc.

Keywords

  • Apoptosis
  • Ca
  • Endoplasmic reticulum
  • Human gastric cancer cells
  • Phospholipase C
  • Safrole

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